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Neurological manifestations in adults with phenylketonuria: new cases and review of the literature

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Abstract

Objective

Phenylketonuria (PKU) is a rare autosomal recessive disease characterised by high plasma phenylalanine levels inducing, if untreated, serious neurological manifestations in children but also, rarely, in adults who stopped their diet. The objective of the study was to describe the neurological manifestations observed in adults with PKU.

Methods

We analysed cases reported in French reference centres for inborn errors of metabolism and cases already reported in the literature.

Results

We report 8 new cases of neurological manifestations and 22 cases in the literature, which occurred in adult PKU patients, associated with chronic or rapid increase of phenylalanine levels, mostly when strict low-phenylalanine diet was stopped early in life. Neurological symptoms consisted in cerebellar ataxia, tremor, brisk reflexes, visual loss, sensory manifestations, and/or headaches. Visual loss was more frequent in the new cases (4/8) of the present series than in the literature (4/22). These neurological complications were associated with leucopathy on brain magnetic resonance imaging (27/29). The start of a low-phenylalanine diet improved or fully reversed neurological manifestations, even in patients with late diagnosis during adulthood.

Conclusion

Neurological manifestations can complicate PKU in adult patients with elevated phenylalanine levels, after long or short period of diet discontinuation. Neurologists should be aware of this diagnosis, and measure phenylalaninemia in case of neurological symptoms associated with non-specific leucopathy on brain MRI. PKU patients should be systematically encouraged to continue their diet and their medical follow-up to avoid neurological complications.

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Author information

Author notes

  1. Paul Jaulent and Sybil Charriere are co-first authors.

Authors and Affiliations

  1. Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Neurologie C, 69677, Bron Cedex, France

    Paul Jaulent & Stéphane Thobois

  2. Hospices Civils de Lyon, Hôpital Cardiovasculaire Louis Pradel, Fédération D’endocrinologie, Maladies métaboliques, diabète Et Nutrition, Groupement Hospitalier Est, 28 avenue Doyen Lépine, 69677, Bron Cedex, France

    Sybil Charriere

  3. INSERM U1060, Laboratoire Carmen, Université Lyon 1, INRA U1235, INSA de Lyon, 69621, Villeurbanne, France

    Sybil Charriere

  4. CENS, Centre de Recherche en Nutrition Humaine Rhône Alpes, 69921, Oullins Cedex, France

    Sybil Charriere

  5. Université Lyon 1 Claude Bernard, Faculté de médecine Lyon EST, 69373, Lyon, France

    Sybil Charriere & Stéphane Thobois

  6. Hospices Civils de Lyon, Centre de référence Des Maladies héréditaires du métabolisme de Lyon, Groupement Hospitalier Est, 69677, Bron Cedex, France

    Sybil Charriere & Alain Fouilhoux

  7. CHU de Nancy, Hôpitaux de Brabois, Centre de référence Des Maladies héréditaires du métabolisme de Nancy, 54511, Vandoeuvre-les Nancy, France

    François Feillet

  8. Centre Hospitalier Régional Universitaire de Lille, Hopital Claude Huriez, Service D’Endocrinologie-Diabétologie-Métabolisme, Hopital Huriez, 59037, Lille, France

    Claire Douillard

  9. CNRS, Institut Des Sciences Cognitives Marc Jeannerod, UMR 5229, 69675, Bron, France

    Stéphane Thobois

Authors
  1. Paul Jaulent
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  2. Sybil Charriere
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  3. François Feillet
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  4. Claire Douillard
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  5. Alain Fouilhoux
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  6. Stéphane Thobois
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Contributions

All authors contributed to the study conception and design. Data collection was performed by PJ, SC, FF, and CD. Analyses of data were performed by PJ and SC. The first draft of the manuscript was written by PJ, SC, and TB, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sybil Charriere.

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Jaulent, P., Charriere, S., Feillet, F. et al. Neurological manifestations in adults with phenylketonuria: new cases and review of the literature. J Neurol 267, 531–542 (2020). https://doi.org/10.1007/s00415-019-09608-2

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  • DOI: https://doi.org/10.1007/s00415-019-09608-2

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